Utilization of peptides as active ingredients for slimming

ABSTRACT

A method of using proteins of the SIRT family or of polypeptide or peptide fragments of SIRT proteins as an active ingredient for slimming, alone or in combination with at least one other active agent, in a cosmetic composition or for the preparation of a pharmaceutical and/or dermatological composition. The invention also includes the use of the peptides for treatment of cellulite and/or used to decrease, eliminate or prevent excess fat beneath the skin.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a division of application Ser. No.: 12/300,597 filedon Nov. 12, 2008; which is the 35 U.S.C. 371 national stage ofInternational application PCT/FRO7/00803 filed on May 11, 2007; whichclaimed priority to French application 0604251 filed May 12, 2006. Theentire contents of each of the above-identified applications are herebyincorporated by reference.

BACKGROUND OF THE INVENTION

The invention concerns the field of cosmetics and pharmaceuticals, inparticular, the field of dermatology.

The purpose of the present invention is the utilization of proteins ofthe SIRT family or polypeptide or peptide fragments of SIRT proteins asan active ingredient for slimming, alone or in combination with at leastone other active agent, in a cosmetic composition or for the preparationof a pharmaceutical and/or dermatological composition. Said peptides areintended, in particular, for treatment of cellulite and/or used todecrease, eliminate or prevent excess fat beneath the skin.

The study of the SIRT genes and the corresponding proteins has providednew therapeutic targets allowing for an intervention in the regulationof the energy metabolism of mammals. The SIRT proteins are part of thefamily of sirtuins, which are NAD+ dependent nuclear proteinsresponsible for deacetylation of histones (Rine J. et Al, Genetics,1979). Several studies in organisms as diverse as C. Elegans or mammalshave shown that there is a relation between energy input and life spanand that the SIRT protein was responsible for this linkage. Thus, areduction in calorie intake increases the life span of yeast (Tissenbaumet Al, Nature, 2001). Furthermore, recent studies have shown that SIRT1causes mobilization of fat in the adipocytes (Picard F. et al, Nature,2004). The SIRT proteins are currently considered to be potentialtherapeutic targets for treatment of dysfunctions or ailments connectedwith obesity, diabetes, or even hyperlipidemia, among others (WO03/061681, US 2005/0164969).

The skin is the integument covering the entire surface of the body, madeup of three distinct superimposed compartments: the epidermis (outerepithelium), the dermis (conjunctive tissue for support) and thehypodermis. The epidermis is a stratified epithelium constituting theexternal structure of the skin and providing its protective function.The dermis is a support tissue involved in the strength, the elasticity,and especially the tonicity of the skin and/or mucous membranes. Beneaththe dermis is a layer of adipose tissues: the hypodermis.

The hypodermis is made up of a layer of white adipose tissue organizedinto lobules attached to the lower part of the dermis by rows ofcollagen fibers and elastic fibers. It is made up of large vacuolizedcells, the adipocytes, almost entirely filled with triglycerides. Thesecells can rapidly change in volume as one loses or gains weight, and canmeasure from 40 to 120 μm in diameter, corresponding to a variation of27 times in volume.

The hypodermal adipose tissue is the largest energy reservoir of thebody. It is able to store lipids in the form of triglycerides by aprocess of lipogenesis, and then release them in the form of fatty acidsand glycerol by a process of lipolysis. It is the equilibrium betweenthese two metabolic pathways which governs adiposity. The lipid reservesof the body are constantly being renewed and have a close relation tothe nutritional intake and energy needs of the body.

If a disequilibrium occurs in the body between the processes oflipogenesis and lipolysis, the volume and the number of adipocytes mayincrease; one speaks of adipocyte hypertrophy and hyperplasia. Excessivedevelopment of the adipose mass may then translate into modifications inthe appearance of the skin, or even evolve into an overweight conditionof the individual, possibly to the point of obesity.

Cellulite, considered to be unsightly, involves a hypertrophy of theadipose cells by overloading with triglycerides and a hyperviscosity ofthe ground substance (by polymerization of polysaccharides). Thesemodifications impede exchanges between the cells and the mobility of theconnective fibers (collagen, elastin and reticulin), which translatesinto water retention, slower venous and lymphatic circulation and lossof skin suppleness. The accentuation of the adipose tissue is localized,especially in women, in the area of the hips, thighs, buttocks, knees,and forearms. The skin takes on a quilted and padded appearance and inthe most advanced stage an “orange peel” appearance, characterized by asuccession of depressions caused by an excessive stretching of theconnective segments and pulling of the epidermis toward the deeptissues.

At present, many research efforts have been carried out to find aneffective way of fighting cellulite and excess fat in general. Manymethods have been used, such as certain medical-surgical techniques likelipoplasty, lymph drainage, mesotherapy, ionophoresis techniques, etc.However, these techniques, while effective, are severe and restricting.Biological ways have been studied to act in a gentle and noninvasivemanner on the mechanisms of formation of subcutaneous fat deposits.

Solutions have been proposed to intervene, in particular, in themetabolism of fatty acids. Cosmetic and pharmaceutical agents thus workon different levels to prevent the appearance of cellulite. For example,they will promote lipolysis, or rather inhibit lipogenesis, that is,reduce the formation of triglycerides.

The main objective of the present invention is to provide a new activeingredient for slimming. In fact, the inventors have succeeded inselecting particular substances having remarkable properties whenapplied to the skin.

Thus, by a first aspect, the object of the present invention is the useof an effective quantity of proteins of the SIRT family or peptide orpolypeptide fragments of the SIRT family or biologically activederivatives of the latter, alone or in combination with at least oneother active agent, to produce a localized slimming effect after beingapplied to the skin, and more particularly to reduce, eliminate orprevent fatty deposits under the skin.

According to one particularly advantage embodiment of the invention, thepeptides belonging to the SIRT family are chosen among the peptidescorresponding to the ID sequences N°:

(1) Gly Ala Gly Ile Ser Thr (2) Gly Ile Pro Asp Phe Arg Ser Pro (3)Gly Ile Pro Asp Phe Arg (4) Gly Ile Pro Asp Phe Arg Ser (5)Gly Leu Tyr Asp Asn Leu Glu (6) Thr Gln Asn Ile Asp Thr Leu

According to one especially preferred embodiment of the invention, thepeptide fragment coming from the SIRT family has the ID sequence N° (5),that is, the sequence Gly Leu Tyr Asp Asn Leu Glu.

The invention also concerns the use of variant forms of these sequencesand/or these fragments. The term “variant” denotes here a polypeptide ora peptide which differs, for example, from the sequence of a referencepeptide while preserving its essential properties. Generally, thedifferences are limited such that the sequences of the reference peptideand those of the variant are quite similar and, in certain regions,identical.

Preferably, the variant forms are those which vary from the referencesequences by the substitution of chemically equivalent (or homologous)amino acids, that is, by the substitution of one residue for another onehaving the same characteristics. Thus, the classical substitutions aredone between Ala, Val, Leu and Ile; between Ser and Thr; between the Aspand Glu acid residues; between Asp and Glu; between Asn and Gln; andbetween the basic residues Lys and Arg; or between the aromatic residuesPhe and Tyr. The term variant also denotes a peptide that differs, forexample, from the sequence of a reference peptide while preserving itsessential properties. Generally, the differences are limited such thatthe sequences of the reference peptide and those of the variant arequite similar and, in certain regions, identical. A variant peptide anda reference peptide can thus differ from the sequence of amino acids byone or more substitutions, additions, deletions in all combinations.

The fragments of SIRT proteins of polypeptide or peptide kind that aredescribed in the present invention also include the use of allbiologically active fragments, or one of their analogues or variants. Bythe phrase biologically active is also meant fragments having an in-vivoor in-vitro activity characteristic of the activity of the compoundaccording to the invention.In the invention, the term “amino acid” refers here to any natural ornonnatural organic acid having the formula:

—NHR—CR—C(O)—O—

where each —R is selected independently between a hydrogen and an alkylgroup having between 1 and 12 carbon atoms. Preferably, at least one —Rgroup of each amino acid is a hydrogen. By the term “alkyl” is meanthere a carbon chain which can be linear or branched, substituted (mono-or poly-) or nonsubstituted; saturated, monosaturated (a double ortriple bond in the chain) or polyunsaturated (two or more double bonds,two or more triple bonds, one or more double bonds and one or moretriple bonds in the chain).The term “peptide” denotes a chain of two or more amino acids joinedtogether by peptide bonds or by modified peptide bonds; a polypeptidedenotes a peptide of rather substantial size.By peptide is meant the natural or synthetic peptide of the invention asdescribed above or at least one of its fragments, whether obtained byproteolysis or synthetically, or any natural or synthetic peptide whosesequence is totally or partially made up of the previously describedpeptide sequence.

In order to improve the resistance to degradation, it may be necessaryto use a protected form of the peptide per the invention. The form ofprotection should obviously be a biologically compatible form and itshould be compatible with a use in the field of cosmetics orpharmaceuticals.

Many forms of biologically compatible protection can be contemplated,and are well known to the practitioner, such as for example acylation oracetylation of the amino-terminal end, or amidation or esterification ofthe carboxy-terminal end. Thus, the invention concerns a use such as wasdefined above, characterized in that the peptide is in a protected formor not. Preferably, one uses a protection based on the acylation oracetylation of the amino-terminal end, or the amidation oresterification of the carboxy-terminal end, or both of these forms. Theamino acid derivatives and the peptide derivatives also include aminoacids and peptides linked together by a pseudo-peptide bond. By“pseudo-peptide bond” is meant all types of bonds able to replace the“classical” peptide bonds.

In the field of amino acids, the geometry of the molecules is such thatthey can in theory be present in the form of different optical isomers.In fact, there exists one molecular conformation of the amino acid (AA)which deviates to the right the plane of polarization of light(dextrorotatory or D-aa conformation), and one molecular conformation ofthe amino acid (aa) which deviates to the left the plane of polarizationof light (levorotatory or L-aa conformation). Nature has chosen fornatural amino acids only the levorotatory conformation. Consequently, apeptide of natural origin will consist only of amino acids of type L-aa.However, chemical synthesis in the laboratory lets one prepare aminoacids having the two possible conformations. Thus, starting with thisbase material, it is possible to incorporate both amino acids in theform of dextrorotatory or levorotatory optical isomers during thepeptide synthesis. And so the amino acids constituting the peptideaccording to the invention can be in the L and D configuration;preferably, the amino acids are in the L form. The peptides according tothe invention can thus be in L, D, or DL form.

The peptides in the present patent can be obtained either by classicalchemical synthesis (in solid phase or in homogeneous liquid phase), orby enzymatic synthesis (Kullman et al., J. Biol. Chem. 1980, 225, 8234)from component amino acids or their derivatives.

The peptides of the invention can likewise be obtained by fermentationof a strain of bacteria, whether modified or not, by genetic engineeringto produce the peptides of the above indicated sequence and theirfragments, or by extraction of proteins of animal or vegetable origin,preferably of vegetable origin, followed by a controlled hydrolysiswhich liberates the peptide fragments of medium size and of small size,according to the invention.

Very many proteins found in plants are likely to contain these sequenceswithin their structure. Guided hydrolysis makes it possible to releasethese peptide fragments. It is possible, but not necessary to realizethe invention, to either extract the particular proteins at first andthen hydrolyze them, or to perform the hydrolysis at first for a crudeextract and then purify the peptide fragments. It is also possible touse certain hydrolyzed extracts without purifying the peptide fragmentsof the invention, yet still making sure of the presence of saidfragments by suitable analytical means.

Other more simple or more complex procedures can be contemplated by thepractitioner who is familiar with the field of synthesis, extraction andpurification of proteins and peptides. Thus, the peptides of theinvention can be of natural or synthetic origin. Preferably, accordingto the invention, the peptides are obtained by chemical synthesis.

In the composition per the invention, the peptides can be a mixture ofpeptide derivatives and/or be made up of amino acid derivatives.

The peptides of the invention, of the composition containing them, havea very effective action on the adipocytes. In fact, they helpsignificantly decrease the quantity of triglycerides contained in theadipocytes of the hypodermis.

This phenomenon is probably due to a blocking of the phenomenon oflipogenesis, that is, blocking of the process of storage oftriglycerides resulting in a hypertrophy of the adipocytes. A control oflipogenesis, that is, the reaction of synthesis of triglycerides in theadipocytes, will help prevent a hypertrophy of the adipocytes, as wellas a succeeding hyperplasia. Thus, when in the course of adipocytedifferentiation the quantity of triglycerides present in the vacuolesdoes not increase, the volume of the adipocytes and their number alsowill not increase. The skin gradually returns to its “normal”appearance. The cellulite tissue develops no further, and the orangepeel effect is diminished. The unattractive appearance of the body issoftened little by little.

The peptides of the invention or the composition containing them thusmakes it possible, primarily because of their particular and pronouncedactivity on adipogenesis, to prevent the appearance of cellulite, andfight its worsening. If cellulite has become established, the peptidesper the invention or the composition containing them will improve theappearance of the skin and, for example, attenuate the “orange peel”appearance. All of these properties make them particularly useful incosmetic and dermatological preparation for slimming purposes.

It is quite obvious that the invention is addressed to mammals ingeneral and more particularly human beings.

According to a second aspect of the invention, the aforesaid peptidescan be used in or for the making of a topical-use composition intendedfor the treatment of cellulite and/or treatment of orange-peel skin. Thepeptides or the composition containing them are advantageously used toreduce, eliminate, or prevent excess fatty deposits beneath the skin.

According to one advantageous embodiment of the invention, the aforesaidpeptides are first solubilized in one or more cosmetically orpharmaceutically acceptable solvents that are classically used by thepractitioner, such as water, ethanol, propylene glycol, butylene glycol,dipropylene glycol, ethoxylated or propoxylated diglycols, cyclicalpolyols, vaseline, glycerol (glycerine, a vegetable oil, or any mixtureof these solvents.

According to another advantageous embodiment of the invention, theaforesaid peptides are first solubilized in a cosmetic or pharmaceuticalvector such as liposomes or adsorbed onto powderlike organic polymers,mineral supports such as talc and bentonite, and more generallysolubilized in, or fixed to, any cosmetically or pharmaceuticallyacceptable vector.

The effective quantity of active ingredient corresponds to the quantityneeded to obtain the desired result.

According to one advantageous embodiment of the invention, the aforesaidpeptides are present, in the compositions of the invention, in aconcentration between around 0.005 and 500 ppm (parts per million), andpreferably in a concentration between around 0.1 and 50 ppm in weight ascompared to the total weight of the final composition.

The composition containing the peptides per the invention can be acosmetic or dermatological or pharmaceutical composition. Preferably,according to the invention, the composition is a cosmetic composition,since it is intended to improve the appearance and general performanceof the skin of the person who uses it.

The composition per the invention is preferably a cosmetic and/ordermatological composition adapted for administration by topical skinroute, containing a cosmetically or pharmaceutically acceptable medium.

These compositions could, in particular, be present in the form of anaqueous, water-alcohol, or oily solution, water-in-oil, or multipleemulsions; they can also be present in the form of suspensions, orpowders, adapted to an application on the skin, the mucous membranes,the lips and/or the hair.

These compositions can be more or less fluid and have the appearance ofa cream, a lotion, a serum, a pomade, a gel, a paste or a foam. They canalso be present in solid form, such as a stick, or be applied to theskin in the form of an aerosol.

These compositions, moreover, contain any additive customarily used inthe contemplated area of application, as well as the adjuvants neededfor their formulation, such as solvents, thickeners, silicones,diluents, antioxidants, colorants, sun screens, self-tanning agents,pigments, ballasts, preservatives, perfumes, deodorants, cosmetic orpharmaceutical active agents, essential oils, vitamins, essential fattyacids, surfactants, film-forming polymers, etc.

For example, in said compositions the peptides per the invention canadvantageously be combined with any other ingredient stimulating theexfoliation of the skin, inhibiting lipogenesis or stimulatinglipolysis, such as derivatives of xanthine. One can mention, forexample, caffeine, theophyllin, theobromin, acephyllin, nicotinate ofxanthinol, diniprophyllin, diprophyllin, etamiphyllin and itsderivatives, etophyllin, proxyphyllin, pentophyllin, propentophyllin,pyridophyllin and bamiphyllin.

In all these cases, the practitioner will make sure that theseadjuvants, active or inactive, as well as their proportions are chosenin such a way as not to harm the advantageous properties sought from thecomposition per the invention. These adjuvants may, for example,correspond to 0.01 to 20% of the total weight of the composition.

If the composition of the invention is an emulsion, the fatty phase canrepresent from 5 to 80% by weight and preferably 5 to 50% by weight ascompared to the total weight of the composition. The emulsifiers andcoemulsifiers used in the composition will be chosen among thoseclassically used in the field in question. For example, they can be usedin a proportion ranging from 0.3 to 30% by weight, in relation to thetotal weight of the composition.

According to a third aspect of the invention, the aforesaid peptides canbe used in or to make a pharmaceutical composition for topical use,intended for the treatment of cellulite and/or for the treatment ofexcess fat deposits beneath the skin.

According to a fourth aspect, the present invention concerns a method ofcosmetic care to achieve a slimming effect. As well as a method ofcosmetic care intended to reduce, eliminate and/or prevent excess fatdeposits beneath the skin, and/or intended to fight cellulite and/orfight the orange-peel skin effect, consisting in applying, topically, tothe zones of skin affected, an effective quantity of at least one of theaforesaid peptides.

The method of slimming cosmetic care also concerns the regularapplication of composition per the invention topically to the zones ofthe face or body being slimmed down, in particular the hips, thebuttocks, the thighs, the stomach, the face.

The advantage of the present invention is that it can provide aneffective topical treatment for adiposity while making use of “gentle”methods.

Other advantages and characteristics of the invention will appear betterfrom a reading of the examples, given by way of illustration and notlimitation.

EXAMPLE 1 Demonstration of the Activity of the Peptides of the Inventionon the Adipocytes

1) Principle of the In-Vitro Test.

Demonstration of the biological activity of the peptides per theinvention was done with the pre-adipocyte cell line 3T3-L1, subjected toa differentiation into mature adipocytes. The number and the size of thelipid vacuoles present in the mature adipocytes are evaluated bymicroscope observation after specific staining with the “Oil Red” stain.

2) Experimental Protocol.

The pre-adipocyte cells 3T3-L1 are seeded in Labteks and maintaineduntil 100% confluence in DMEM 10% SVF culture medium. The cells aretreated with the peptide of sequence ID N° (5), representative of thefamily of peptides per the invention, placed in 1% solution à 1%starting with a solution of 50 ppm. Nontreated controls were prepared inparallel.

Once confluence is achieved, the cells are cultivated in the presence ofdifferentiation inducers (IBMX, dexamethasone and insulin), so as tobring about the final differentiation into mature adipocytes. Thedifferentiated adipocytes are further incubated for 3 hours with thepeptide being tested in a concentration of 1%. Nontreated controls wereprepared in parallel.

The adipocytes are then fixed for 10 minutes in a 4% formol and NaClsolution, after which the “Oil Red” stain solution (Sigma, O-0625) isapplied for 15 minutes. The cells are then rinsed with warm water andmounted on slides, in hydrophilic medium (Aquatex). The observation isdone under an optical microscope.

3) Results

The results of the observation of the cells show that the matureadipocytes of the nontreated controls have a voluminous spherical shapeand show a major accumulation of intra-cytoplasmic lipid vesicles; onthe other hand, the mature adipocytes treated by a solution containingthe peptide of the invention have a less rounded morphology and aclearly diminished content of intra-adipocyte lipid vesicles.

Peptide of Control sequence ID N^(o) (5) Size/number of lipid droplets++++ ++

4) Conclusions

The solution containing the peptide of the invention proves to beparticularly effective in the process of limitation of adipocytehypertrophy. Thus, it allows for an elimination of the triglyceridescontained in the intra-adipocyte vesicles.

EXAMPLE 2 Preparation of Compositions 1—Slimming Cream

% by Commercial names INCI Names mass PHASE A Montanov 68 CetearylAlcohol (and) 5.00 Cetearyl Glucoside Squalane Squalane 2.50 DUB IPPIsopropyl Palmitate 3.50 Eutanol G Octyldodecanol 1.50 PhenonipPhenoxyethanol (and) Methyl- 0.50 paraben (and) Ethylparaben (and)Butylparaben (and) Propylparaben (and) Isobutylparaben PHASE BDemineralized water Aqua (Water) Qsp Glycerine Glycerin 3.00 ButyleneGlycol Butylene glycol 3.00 PHASE C Simulgel EG SodiumAcrylate/Acryloyldi- 0.60 methyl Taurate Copolymer (and) Isohexadecane(and) Polysorbate 80 PHASE D Peptide per 1.25 ppm the invention PerfumePerfume (Fragrance) Qsp Colorant Qsp

Operating Procedure

The constituents of phase A are melted at 75° C. and the constituents ofphase B heated to 75° C. Phase A is emulsified in B, then the mixture iscooled below 40° C. Phases C and D are then added under constantagitation.

2—Firming-Slimming Spray

% by Commercial names INCI Names mass PHASE A Emulgade SEV GlycerylStearate (and) 4.60 Ceteareth-20 (and) Ceteareth-12 (and) CetearylAlcohol Eumulgin B2 Ceteareth-20 1.40 Cetiol OE Dicaprylyl Ether 3.00DUB B1215 C12-C15 Alkyl Benzoate 5.00 Phenonip Phenoxyethanol (and)Methyl- 0.50 paraben (and) Ethylparaben (and) Butylparaben (and)Propylparaben (and) Isobutylparaben DUB ININ Isononyl Isononanoate 5.00PHASE B Demineralized water Aqua (Water) 15.00 Glycerine Glycerin 3.00PHASE C Demineralized water Aqua (Water) Qsp PHASE D Peptide per 1.50ppm the invention Perfume Perfume (Fragrance) qsp Colorant qsp

Operating Mode

The constituents of phase A and phase B are heated separately to 65° C.; phase B is incorporated in phase A under agitation. The temperature ofthe mixture is increased to 83° C., then it is cooled to the phaseinversion temperature. Phase C is then added. The active ingredient isincorporated when the temperature reaches less than 40° C. It is thenpossible to add fragrances and/or colorants.

3—Firming-Slimming-Anti-Cellulite Gel

% by Commercial names INCI Names mass 1. Carbopol Ultrez 10 ( 2% )Carbomer 25.00 2. Demineralized water Aqua (Water) ) Qsp 3. DUB DIOLMethyl Propanediol 3.00 4. EDTA Tetrasodium EDTA 0.10 5. Glydant PlusLiquid DMDM Hydantoïn 0.20 (and) Iodopropynyl butylcarbamate 6. Peptideper the invention 1.25 ppm 7. TEA Triethanolamine 0.50 8. PerfumePerfume (Fragrance) Qsp 9. Water-soluble colorant Qsp

Operating Mode

The Carbopol gel is prepared at 2%. The ingredients are added in theorder enumerated above, under agitation. The mixture is then neutralizedwith the TEA. The fragrance and colorants are added if necessary.

1. A method of reducing excess fat deposits beneath the skin, and/ortreating cellulite and/or treating the orange-peel skin effect,comprising: administering an effective amount of a peptide consisting ofthe sequence Gly Leu Tyr Asp Asn Leu Glu (SEQ ID NO 5) as an activeslimming agent, alone or in combination with at least one other activeagent, in a cosmetic, pharmaceutical and/or dermatological compositionto a subject in need thereof.
 2. The method according to claim 1,wherein the effective amount treats cellulite and/or orange peel skin;and/or to reduces excess fat deposits beneath the skin.
 3. The methodaccording to claim 1, wherein the composition further comprises acosmetically acceptable lipolytic agent.
 4. The method according toclaim 3, wherein the lipolytic agent is selected from the groupconsisting of caffeine, acephyllin, nicotinate of xanthinol,diniprophyllin, diprophyllin, etamiphyllin, etophyllin, proxyphyllin,pentophyllin, propentophyllin, pyridophyllin, bamiphyllin, theophyllin,and theobromin.
 5. The method according to claim 1, wherein the peptidehas at least one functional group protected by a protecting group formedby an acylation or an acetylation of the amino-terminal end, or anamidation or an esterification of the carboxy-terminal end, or both. 6.The method according to claim 1, wherein the peptide is present in thecomposition in a concentration between around 0.005 and 500 ppm.
 7. Themethod according to claim 1, wherein the peptide is first solubilized inone or more cosmetically or pharmaceutically acceptable solvent selectedfrom the group consisting of water, ethanol, propylene glycol, glycerol,butylene glycol, dipropylene glycol, ethoxylated or propoxylateddiglycols, cyclical polyols, vaseline, a vegetable oil, and mixturesthereof.
 8. The method according to claim 1, wherein the peptide isfirst solubilized in a cosmetic or pharmaceutical vector or a mineralsupport.
 9. The method according to claim 1, wherein the peptide isfixed to a cosmetically or pharmaceutically acceptable vector.
 10. Themethod according to claim 1, wherein the peptide is administered in agalenical form adapted for application on the skin, the mucousmembranes, the lips and/or the hair selected from the group consistingof aqueous solutions, water-alcohol solutions, oily solutions,oil-in-water emulsions, water-in-oil emulsions, multiple emulsions,suspensions, shampoos, sticks, sprays and powders.
 11. The methodaccording to claim 1, wherein the composition is administered topicallyto the skin of the subject.